This invention relates to coating of stents. These stents contain a medicated coating composed of an immuno-suppressing drug dispersed in a polymer matrix. The purpose of the coating (about 10 to 15 xcexcm thick) is to slowly release medication that will inhibit the proliferation of smooth cells and therefore reduce risk of restenosis.
Three elements are required for a successful coating of a stentxe2x80x94the resin, the drug, and the application process. There have been identified a number of generic classes of materials, which can be considered as possible binders for the coating formulation. A process for applying these coatings in a reproducible fashion is required in order to evaluate the coatings. This invention deals with the development of such a process. Processes for coating stents are described, for instance, in Ser. No. 09/061,568, filed Apr. 16, 1998, and Ser. No. 09/512,432 filed Feb. 25, 2000, both of which are assigned to a common assignee and are incorporated herein by reference.
Thus, the objective of this invention is to produce a thin (around 10 xcexcm) conformal coating of polymer containing drug on the struts of the stent. The coating should encapsulate the struts of the stent so that the danger of small pieces of coating lifting or breaking off is eliminated. At the same time the coating had to be applied in such a way so as not to fill the openings between the struts or in any way obstruct the mechanical performance of the stent.
In summary, a stent is positioned on an undersized mandrel and the stent is coated with an excess of a polymer and drug solution. The stent is rotated to spin off the excess of the coating. The stent is then moved into a new, clean position on the mandrel. This forward movement is believed to remove excess solution from the inside of the stent. The process is repeated a few times, after which time the coating is already dry and non-sticky. This process forms a conformal coating. It should be understood that in terms of the process, important polymer solution parameters include viscosity, solvent evaporation rate and several others. The actual type of coating polymer is not as important as how the surface of the stent is treated, according to the steps described herein.
According to the present invention, the following steps are followed for coating a drug to a stent.
1. The stents are cleaned in a beaker to which about 20 ml solvent is added.
2. Cover with a watch glass.
3. Sonicate the stent/solvent beaker for about 1 minute.
4. Leave stents in solvent until use.
5. Clean 1.27 mm diameter mandrel by wiping with acetone. Set aside to dry on a clean surface.
6. Place stent on mandrel by using end of mandrel to insert into one end of the stent and slowly pushing onto the mandrel from the solution.
7. By tapping the mandrel from the opposite end, allow the stent to slide over the mandrel to the opposite end of the mandrel. One can also use a scalpel to slowly push the stent down; it should move freely.
8. Insert mandrel into mandrel chuck on apparatus (see FIG. 22)
9. Once on the apparatus, turn on the mandrel motor and rotate at high speed for a few seconds while blowing the stent with dry, clean nitrogen gas. This serves to dry the stent from any residual solvent
10. Weigh out a silicone polymer solution into a vial.
11. Weigh out the (rapamycin) drug and put into vial.
12. Add solvent (e.g. xylene) to vial. Record weights of all components.
13. Seal the vial with a screw top (note: vial top should be compatible with the solvents in use) and then shake the vial to mix the components. Sonicate the mixture for about 5 minutes.
14. Using a plastic syringe, transfer a small amount (about 0.5 ml) of the solution onto the stent by dropping the solution over the stent on the mandrel, thoroughly coating the stent.
15. Immediately turn on the mandrel motor and rotate at about 4000 RPM. This serves to throw off any excess solution from the stent and provide the proper distribution of the solution on the stent surface. Turn the motor on and off in pulses of about 1 second. This process serves to constantly accelerate/decelerate the stent to keep the stent moving relative to the mandrel so that it avoids sticking to the mandrel.
16. After about 15 seconds, turn off the motor and move the stent about one stent length along the mandrel to a clean section. Run the mandrel motor and pulse the motor for about 10 seconds. Repeat this step two (or more) times.
17. Turn off the motor and move the stent about 2 stent lengths down the mandrel to a clean section. Turn on the motor and run it at full speed while blowing the stent with clean, dry nitrogen for a time of about 20 seconds.
18. Turn off the motor; slowly move the stent forward to push it off the mandrel into a receiving vial.
19. Remove the mandrel from the apparatus, clean, and prepare for the next run.
20. A preferred polymer is an RTV (room temperature vulcanization, i.e., curing) silicone, which means that it cures at room temperature in about 24 hours. Moisture is required for the cure. Therefore, place the stent in a very moist environment. One easy way to do this is to use a forced air oven and place a container of water at the bottom of the oven. Maintain the oven temperature at ambient or slightly above. The forced air absorbs the moisture by evaporation from the container and cures the polymer on the stent.